There is no readily available method that can be used to precisely assess both regional myocardial perfusion and function in humans. It has been recently demonstrated by the principal investigator and others that myocardial contrast echocardiography can be utilized to define zones of decreased perfusion. Further, two- dimensional echocardiography has also been used by the principal investigator and others for quantitating regional myocardial function. This proposal aims at developing these techniques using computer analysis for simultaneous assessment of regional perfusion and function, first in the animal model, and later in humans. An attempt will be made to understand the relationship between myocardial contrast parameters and regional myocardial blood flow as measured by radiolabeled microspheres and mean coronary transit times using technetium labeled red cells. Algorithms will be developed to measure absolute regional myocardial blood flow derived from parameters obtained from the washout of contrast from the myocardium. It is hoped that this research will provide an in-depth understanding of the kinetics of microbubbles through the myocardium at different coronary flow rates and the effect of flow on the microbubbles. The optimal contrast agent and the optimal method for injection of the agent without causing a hyperemic response will be developed. The effect of this agent on normal and ischemic human myocardium will be studied. Although methods for measuring regional myocardial function have been previously described, there are limitations in these methods which mostly relate to defining the center of mass in an ischemic ventricle and overall translation of the heart. This proposal defines a new approach for quantifying regional myocardial function using a sophisticated computer algorithm which is independent of the center of mass and is not affected by cardiac translation. Using these techniques, we aim to study the relationship between transmural and endocardial blood flow and regional myocardial function over varying degrees of coronary blood flow. It is also proposed to estimate coronary flow reserve in humans prior to and following coronary angioplasty to determine if changes in coronary flow reserve correlate with the success of coronary angioplasty and the restenosis rate following the procedure. It is hoped that these methods can be used to assess regional myocardial perfusion and function simultaneously in humans using tow-dimensional echocardiography.